The role of poxviruses, subviral particles isolated from virions or purified poxviral DNA in causing abnormal proliferation or neoplastic transformation of human and murine cells will be investigated. The structure and replication of ortho and paravaccinia DNAs will be studied in order to define: (a) The nature of the viral chromosomal structure and (b) the viral "replisome", in order to gain insight into the structure and replication of intrinsically more complex eukaryotic cell chromosomes. Alterations in cellular membranes following infection with various vaccinia strains will be compared and defined to: (a) Determine how such alterations affect cell growth and cell-cell recognition; (b) function in providing "targets" recognized by the host's immune system. Restriction enzyme analysis and molecular hybridization techniques will be used to probe the genetic relatedness of poxviruses and their diversification in nature. This will provide the basis for future studies of the genetic information needed for determining host range specificity, pathogenicity and cell proliferation or killing after infection of cells with poxviruses.